Train of Four Monitoring Device

Assessment of neuromuscular blockade during anesthesia is achieved using the Train of Four (TOF) monitoring technique. However, current devices are limited to conditions in which the hand can move freely during operation. The goal of this project was to design, prototype, and test a device which extends the TOF technique to conditions where movement is restricted. Interviews were conducted with stakeholders to better understand the need for this device and to get feedback on preliminary designs. The resulting device consists of a thumb-mounted balloon, which converts the force due to thumb twitches into pressure, which then acts as the physical analog to muscle response. This pressure is transduced and analyzed to produce a TOF count and TOF ratio. A prototype was constructed and tested on human subjects with different hand geometries.

Cisatracurium dosing in a patient with hyperthermia

Purpose A case report involving varying cisatracurium dosing requirements in a hyperthermic patient undergoing prone ventilation who subsequently received active cooling as part of targeted temperature management is presented. Summary Cisatracurium is known to be primarily metabolized via pH- and temperature-dependent Hofmann elimination. Previous reports in the literature described cases of decreased dosing requirements for both cisatracurium and its parent compound, atracurium, for patients in hypothermic states. While augmented atracurium dosing requirements in hyperthermic states have been reported, a literature search found no such reports concerning cisatracurium administration. In the case described here, a patient was initiated on cisatracurium for treatment of symptoms suggestive of acute respiratory distress syndrome (ARDS) and septic shock. An initial dosing requirement of 12 µg/kg/min (adjusted to a goal of 2–4 twitches per train-of-four monitoring) was needed to achieve adequate paralysis while the patient remained hyperthermic (a bladder temperature of 40.1°C). This cisatracurium infusion rate exceeded maximum reported and maximum institutional infusion rates (10 µg/kg/min). After initiation of cooling and lowering of the bladder temperature to 37.8°C, the cisatracurium rate requirement decreased to 5 µg/kg/min. Conclusion A hyperthermic patient thought to have ARDS and septic shock required a high rate of cisatracurium infusion for adequate paralysis during mechanical ventilation. The cisatracurium did not appear to cause prolonged neuromuscular blockade.

Low-frequency Neuromuscular Depression Is a Consequence of a Reduction in Nerve Terminal Ca2+ Currents at Mammalian Motor Nerve Endings

Background: The decline in voluntary muscle contraction during low-frequency nerve stimulation is used clinically to assess the type and degree of neuromuscular block. The mechanism underlying this depression is unknown. Methods: Simultaneous electrophysiological measurements of neurotransmitter release and prejunctional Ca2+ currents were made at mouse neuromuscular junctions to evaluate the hypothesis that decreases in nerve terminal Ca2+ currents are responsible for low-frequency depression. Results: Under conditions generally used to measure Ca2+ currents at the neuromuscular junction, increasing the frequency of nerve stimulation briefly from 0.017 to 0.1–1 Hz caused a simultaneous reduction in the release of the neurotransmitter acetylcholine to 52.2 ± 4.4% of control and the Ca2+ current peak to 75.4 ± 2.0% of control (P < 0.001, n = 5 experiments for both measurements, mean ± SEM for all data). In conditions used for train-of-four monitoring (4 stimuli, 2 Hz), neurotransmitter release declined to 42.0 ± 1.0% of control and the Ca2+ current peak declined to 75.8 ± 3.3% of control between the first and fourth stimulus (P < 0.001, n = 7 experiments for both measurements). Depression in acetylcholine release during train-of-four protocols also occurred in the absence of neuromuscular-blocking drugs. Discussion: The results demonstrate that neuromuscular depression during train-of-four monitoring is due to a decline in nerve terminal Ca2+ currents, hence reducing the release of acetylcholine. As similar processes may come into play at higher stimulation frequencies, agents that antagonize the decline in Ca2+ currents could be used to treat conditions in which neuromuscular depression can be debilitating.